The long-range goal of this proposal is to elucidate the cellular mechanisms which reduce embryo survival in vivo. The project uniquely integrates emerging techniques of cell and developmental biology to evaluate the growth potential of living mammalian embryos. The research plan has three specific aims: 1) to determine oxygen consumption rates (Q02) of single preimplantation mouse and pig embryos and to correlate these data with in vivo survivability after subsequent embryo transfer to foster mothers; 2) to use non-invasive correlative assays of oxidative metabolism in conjunction with embryo transfer to assess the efficacy of embryo Q02 as an accurate indicator of embryo viability; 3) to use invasive correlative assays to assess the utility of embryo Q02 as a rapidly measurable parameter to accurately predict embryo viability. The proposed experiments will take a highly integrated approach using physiological, biochemical and embryo manipulation techniques to assess embryo viability in vitro and in vivo. Procedures to be used include: measurement of oxygen consumption rate and trans-trophetodermal Na+ influx, metabolic radiolabeling, fluorescence vital staining, embryo microinjection, culture and transfer. The objectives clearly support the need to develop techniques to assess embryo viability in a non-perturbing manner. Specifically, results of this project may suggest new avenues for reducing embryonic mortality by revealing the basic cellular mechanisms which specify the normal processes of embryogenesis and, may lead to the development of methodologies, e.g. Q02, to accurately assess embryo viability for clinical application in human IVF-ET programs.